背景:遗传因子X(FX)缺乏症(HFXD)是一种常染色体隐性遗传性罕见出血性疾病,可导致FX蛋白缺陷。根据缺陷的程度,患者可能面临危及生命的出血风险.FX缺乏症的历史治疗包括凝血酶原复合物浓缩物,这会增加血栓形成的风险,和新鲜的冷冻血浆,会导致容量超负荷和输血反应。血浆衍生FX(pdFX),单因素,高纯度,高效人类FX治疗,2015年在美国获得批准,2016年在欧洲获得批准,用于HFXD患者的按需治疗和出血事件预防以及围手术期管理.
方法:五项研究检查了轻度(血浆FX活性[FX:C]≥5IU/dL)患者使用pdFX,中等(FX:C≥1且<5IU/dL),或重度(FX:C<1IU/dL)HFXD进行了审查:TEN01,TEN02和TEN03是前瞻性的,开放标签,多中心,非随机研究,TEN05和TEN06是多中心回顾性研究。
结果:当用作按需治疗时,调查人员认为pdFX成功治疗41/42(97.6%),TEN01、TEN02和TEN05分别有2/3(66.6%)和79/79(100%)出血。预防性使用时,在TEN02和TEN05中,pdFX分别在9名(100%)和8名(100%)患者中被判定为“极好”。还评估了围手术期治疗和药代动力学。pdFX是安全的,耐受性良好。
结论:一起,这些研究支持使用pdFX按需治疗出血,常规预防,HFXD患者的围手术期出血处理。
BACKGROUND: Hereditary factor X (FX) deficiency (HFXD) is an autosomal recessive rare bleeding disorder that leads to defects in the FX protein. Depending on the degree of deficiency, patients may be at risk of life-threatening bleeding episodes. Historical treatments for FX deficiency include prothrombin complex concentrates, which can increase the risk of thrombosis, and fresh frozen plasma, which can cause volume overload and transfusion reactions. Plasma-derived FX (pdFX), a single-factor, high-purity, high-potency human FX treatment, was approved in 2015 in the United States and in 2016 in Europe for on-demand treatment and prophylaxis of bleeding episodes and perioperative management of patients with HFXD.
METHODS: Five studies that examined the use of pdFX in patients with mild (plasma FX activity [FX:C] ≥5 IU/dL), moderate (FX:C ≥1 and <5 IU/dL), or severe (FX:C < 1 IU/dL) HFXD were reviewed: TEN01, TEN02 and TEN03 were prospective, open-label, multicentre, nonrandomised studies, and TEN05 and TEN06 were multicentre retrospective studies.
RESULTS: When used as an on-demand treatment, pdFX was judged by investigators to be successful in treating 41/42 (97.6%), 2/3 (66.6%) and 79/79 (100%) bleeds in TEN01, TEN02 and TEN05, respectively. When used prophylactically, pdFX was judged \'excellent\' for the prevention of bleeds in nine (100%) and eight (100%) patients in TEN02 and TEN05, respectively. Perioperative treatment and pharmacokinetics were also assessed. pdFX was safe and well tolerated.
CONCLUSIONS: Together, these studies support the use of pdFX for on-demand treatment of bleeding, routine prophylaxis, and perioperative management of bleeding in patients with HFXD.